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  • 551.
    Winbo, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Long QT syndrome in Sweden: founder effects and associated cardiac phenotypes2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: We aimed to increase the knowledge regarding the familial arrhythmogenic disorder Long QT Syndrome (LQTS) and its recessive variant Jervell and Lange-Nielsen Syndrome (JLNS) in Sweden, including prevalences and clinical phenotypes. A specific focus was directed towards two KCNQ1 mutations –p.Y111C and p.R518X- commonly identified in Swedish LQTS index cases.

    Methods: Cases and families with LQTS (p.Y111C or p.R518X) and JLNS were recruited via regional clinical practices, national referrals to the Clinical Genetics laboratory, Umeå University Hospital, and a national inventory. Molecular genetics methods were used for case ascertainment. Clinical data was obtained via medical records, a questionnaire, and/or an interview. Electrocardiograms were manually assessed. In p.R518X heterozygotes intra-familial phenotypic variability (QTc and cardiac events) was assessed by analysis of sequence variants (modifier genes). The origins of the mutations p.Y111C and p.R518X were investigated using genealogical and haplotype analysis (microsatellite markers). In families sharing a common haplotype mutation age and associated prevalence was analyzed using ESTIAGE and DMLE computer software.

    Results: We identified p.Y111C (170 mutation-carriers) and p.R518X (101 mutation-carriers) as two major causes of LQTS/JLNS in Sweden. LQTS phenotype was revealed to be relatively benign in p.Y111C and p.R518X (annual incidence of life-threatening cardiac events, before therapy 0.05% and 0.04%, respectively). Gender-specific effects of genetic modifiers on phenotypic expression were seen. A founder origin, approximately 600-700 years ago in two northern river valleys was established for p.Y111C and p.R518X, and a high prevalence of LQTS founder descendants suggested. A minimum JLNS prevalence of 1:200 000 in preadolescent Swedish children was revealed. JLNS phenotype was mainly severe, with a cumulative incidence of life-threatening cardiac events of 53% (annual incidence rate before therapy 5%) and four sudden deaths. Possible founder effects regarding four KCNQ1 mutations; p.Y111C (8%), p.R518X (50%), c.572_576del (17%) and p.Q530X (8%) together explained 83% of the JLNS mutation-spectrum in Sweden, consisting of 8 KCNQ1 mutations.

    Conclusion: The high prevalence of p.Y111C- and p.R518X-related LQTS as well as JLNS revealed in Sweden could be explained by the combination of mild clinical phenotypes in heterozygotes and strong founder effects present during the population development of northern Sweden. Increased knowledge regarding the occurrence of LQTS and JLNS as well as mutation- and/or genotype-specific data constitute prerequisites for possible improvement of patient management.

  • 552.
    Winbo, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vestibular dysfunction is a clinical feature of the Jervell and Lange-Nielsen Syndrome2015In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 49, no 1, p. 7-13Article in journal (Refereed)
    Abstract [en]

    Objectives. To investigate the possible association between Jervell and Lange-Nielsen Syndrome (JLNS) genotype and vestibular dysfunction. Design. In 15 cases with JLNS, clinical data obtained from a semi-structured interview and full medical records were reviewed and post-rotatory nystagmus testing was performed. Results. All genotyped cases (n = 14) had double KCNQ1 mutations. Symptoms of impaired balance were reported in 14/14 deaf JLNS cases. Gross motor developmental delay (not walking without support at 18 months of age) was seen in 11/12 cases with available data (mean age for walking: 24 months). A pathologic post-rotatory test was seen in 9/9 tested subjects, and in 3 subjects clinical testing had been performed showing complete lack of vestibular function. Vestibular dysfunction was seen in deaf JLNS cases with (n = 5) and without (n = 9) cochlear implants, including subjective symptoms (5/5 vs. 9/9) and gross motor developmental delay (5/5 vs. 6/8). Conclusions. We identified a high frequency of symptoms and signs associated with vestibular dysfunction in deaf JLNS cases, irrespective of previous cochlear implantation. Disruption of endolymph homeostasis in the inner ear, including cochlea and vestibular system, by profound KCNQ1 function loss is the proposed mechanism.

  • 553.
    Winbo, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Norberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Nordin, Charlotte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Diamant, Ulla-Britt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Persson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The Swedish long QT syndrome R518X/KCNQ1 founder population- origin and clinical phenotype: phenotypic variability partly explained by gender-specific effects of sequence variants in the NOS1AP geneManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Genetic modifiers have been proposed to explain phenotypic variability in the long QT syndrome (LQTS). We investigate the origin and phenotype of the worldwide common R518X/KCNQ1 mutation in Sweden, as well as possible associations between p.R518X-LQTS phenotype and previously reported modifying sequence variants in the NOS1AP, KCNH2, KCNE1, SCN5A and KCNQ1(3’UTR) genes.

    Methods and Results: We identified 19 p.R518X families (101 mutation-carriers, whereof 15 Jervell and Lange-Nielsen (JLNS) cases and 86 LQTS cases). Analyses of microsatellite markers, genealogy and mutation age (ESTIAGE) identified a common northern origin ~700 years ago for 17/19 families and a high prevalence of Swedish p.R518X heterozygotes was suggested (DMLE). 

    Clinical phenotype ranged from severe in JLNS to relatively benign in LQTS (QTc 576±61 ms vs. 462±34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%).

    In p.R518X-LQTS males, two NOS1AP variants rs12143842 and rs16847548 were associated with a 29 ms QT prolongation (p=0.004), explaining 27% of QTc variability.

    Three derived 3’UTR-KCNQ1 variants, previously shown to suppress gene expression in an allele-specific manner, were found to segregate with the founder mutation.

    Conclusion: The R518X/KCNQ1 mutation is a Swedish founder mutation presenting with an expectedly severe phenotype in JLNS and an unusually mild phenotype in LQTS, although intra-familial variability remained. Gender-specific effects of NOS1AP sequence variants explained over a fourth of QTc variance in p.R518X-LQTS males, warranting further studies. Repressive 3’UTR-KCNQ1 sequence variants segregating within the founder haplotype could possibly contribute to its relative benignancy.

  • 554.
    Winbo, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Nordin, Charlotte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Diamant, Ulla-Britt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Persson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jensen, Steen M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families2014In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 14, p. 22-Article in journal (Refereed)
    Abstract [en]

    Background: The R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome-JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p. R518X mutation. Methods: The study included 19 Swedish p. R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software). Results: Clinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 +/- 61 ms vs. 462 +/- 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%). A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p. R518X heterozygotes was suggested (similar to 1: 2000-4000). Conclusions: R518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.

  • 555. Wit, J. M.
    et al.
    Ranke, M. B.
    Albertsson-Wikland, K.
    Carrascosa, A.
    Rosenfeld, R. G.
    Van Buuren, S.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schoenau, E.
    Audi, L.
    Hokken-Koelega, A. C. S.
    Bang, P.
    Jung, H.
    Blum, W. F.
    Silverman, L. A.
    Cohen, P.
    Cianfarani, S.
    Deal, C.
    Clayton, P. E.
    de Graaff, L.
    Dahlgren, J.
    Kleintjens, J.
    Roelants, M.
    Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models2013In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 79, no 5, p. 257-270Article, review/survey (Refereed)
    Abstract [en]

    The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.

  • 556. Wolthers, Benjamin Ole
    et al.
    Mogensen, Pernille R.
    Frandsen, Thomas L.
    Abrahamsson, Jonas
    Behrendtz, Mikael
    Heyman, Mats
    Lohi, Olli
    Norén-Nyström, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ruud, Ellen
    Schmiegelow, Kjeld
    Insulin-dependent diabetes: a chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia2019In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 66, no 1, article id e27437Article in journal (Refereed)
    Abstract [en]

    Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL) treatment, significantly associated with asparaginase use, and may be followed by severe complications such as acute hyperglycaemia, need for mechanical ventilation, pseudocysts, and death. Here, we provide novel data on seven patients diagnosed with diabetes after pancreatitis and still requiring insulin treatment after a median follow-up of 4.2 years (range: 1.7-9.2). We describe the clinical course of pancreatitis and illustrate the association between pancreatic pseudocysts, older age, and development of insulin-dependent diabetes. Together, this study documents the persisting burden of pancreatitis in childhood ALL and underlines the need for plasma glucose level monitoring.

  • 557. Wopereis, Harm
    et al.
    Van Ampting, Marleen
    Candy, David C. A.
    Peroni, Diego
    Vandenplas, Yvan
    Fox, Adam
    Nijhuis, Manon M. Oude
    Harthoorn, Lucien
    Michaelis, Louise J.
    Knol, Jan
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gut Microbiota Composition of Non-IgE Mediated Cow's Milk Allergic Infants before and after Dietary Management with a Synbiotics-Supplemented Amino Acid-Based Formula2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 2, p. AB53-AB53Article in journal (Refereed)
  • 558.
    Zachrisson, I
    et al.
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Brismar, K
    Department of Endocrinology and Diabetology, Karolinska Hospital and Institute, Stockholm, Sweden.
    Carlsson-Skwirut, C
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wallensteen, M
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Bang, P
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.2000In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 10, no 6, p. 324-31Article in journal (Refereed)
    Abstract [en]

    Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.

  • 559.
    Zachrisson, I
    et al.
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wallensteen, M
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Brismar, K
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Insulin-like growth factor binding protein-1 as glucose regulator in adolescent boys with type 1 diabetes.2000In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, no 9, p. 1044-9Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S-Insulin, S-GH, S-IGF-I and S-IGFBP-1 were analysed. B-Glucose was analysed hourly at bedside. One week before and 1 wk after the 24-h study period the participants performed self-monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24-h profile of B-Glucose, insulin, IGFBP-1 and GH, we found a significant positive correlation between B-Glucose and log IGFBP-1 (r = 0.5, p = 0.005) and an inverse correlation to insulin (r = -0.5, p = 0.004) but no correlation to logGH (r = -0.04, p = 0.831). In multiple regression analysis, B-Glucose was still significantly correlated to log IGFBP-1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B-Glucose over a longer period during normal daily activity (p = 0.02), but not over the 24-h study period. CONCLUSION: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood-glucose and IGFBP-1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF-I influences the glucose metabolism.

  • 560. Zaman, S.
    et al.
    Lange, S.
    Jennische, E.
    Aamir, K.
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hanson, L. A.
    The antisecretory factor - an efficient tool for rapid recovery from early childhood diarrhoea2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 9, p. E391-E391Article in journal (Refereed)
  • 561. Zaman, Shakila
    et al.
    Aamir, Khalida
    Lange, Stefan
    Jennische, Eva
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hanson, Lars A.
    Antisecretory factor effectively and safely stops childhood diarrhoea: a placebo-controlled, randomised study2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 6, p. 659-664Article in journal (Refereed)
    Abstract [en]

    Aim

    We studied the response to high doses of egg yolk containing antisecretory factor (B221((R)), Salovum((R))) in young children with acute diarrhoea, presenting to the Children's Hospital, Lahore, Pakistan.

    Methods

    In a randomised, placebo-controlled trial, 36 children aged 7 to 60months with acute diarrhoea of unknown aetiology, with mild-to-moderate dehydration, were randomised to the Salovum((R)) or placebo groups. Initially, 16 grams of Salovum((R)) or ordinary egg yolk (placebo) mixed in oral rehydration salts was given, followed by 8g every 5h until recovery. The number and consistency of stools were recorded.

    Results

    The two groups were comparable in age, gender, duration of diarrhoea, hydration and nutritional status, although the proportion with watery stools was higher in the Salovum((R)) group (p=0.04). Reduction in the frequency of stools was seen at 7 versus 18h (p<0.0001) and normalising of stool consistency was 10 versus 18h, p<0.03) in the Salovum((R)) and placebo groups. The overall effect was 35 versus 70h in the two groups (p=0.001). No side effects were reported.

    Conclusion

    High doses of AF in the form of Salovum((R)) effectively and safely reduce childhood diarrhoea of a likely broad aetiology.

  • 562.
    Zamir, Itay
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Abrahamsson, T.
    Ahlsson, F.
    Hallberg, B.
    Pupp, I.
    Stjernkvist, K.
    Serenius, F.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Early-life hyperglycemia in extremely preterm infants affects neurodevelopment at 6 years of age2016In: EUROPEAN JOURNAL OF PEDIATRICS, ISSN 0340-6199, Vol. 175, no 11, p. 1440-1440Article in journal (Refereed)
  • 563.
    Zamir, Itay
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Edstedt Bonamy, Anna-Karin
    Mohlkert, Lilly-Ann
    Norman, Mikael
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm2019In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 86, no 1, p. 115-121Article in journal (Refereed)
    Abstract [en]

    Background: Adverse developmental programming by early-life exposures might account for higher blood pressure (BP) in children born extremely preterm. We assessed associations between nutrition, growth and hyperglycemia early in infancy, and BP at 6.5 years of age in children born extremely preterm.

    Methods: Data regarding perinatal exposures including nutrition, growth and glycemia status were collected from the Extremely Preterm Infants in Sweden Study (EXPRESS), a population-based cohort including infants born <27 gestational weeks during 2004–2007. BP measurements were performed at 6.5 years of age in a sub-cohort of 171 children (35% of the surviving children).

    Results: Higher mean daily protein intake (+1 g/kg/day) during postnatal weeks 1–8 was associated with 0.40 (±0.18) SD higher diastolic BP. Higher mean daily carbohydrate intake (+1 g/kg/day) during the same period was associated with 0.18 (±0.05) and 0.14 (±0.04) SD higher systolic and diastolic BP, respectively. No associations were found between infant growth (weight, length) and later BP. Hyperglycemia and its duration during postnatal weeks 1–4 were associated primarily with higher diastolic BP z-scores.

    Conclusions: These findings emphasize the importance of modifiable early-life exposures, such as nutrition and hyperglycemia, in determining long-term outcomes in children born extremely preterm.

  • 564.
    Zamir, Itay
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Tornevi, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Abrahamsson, Thomas
    Ahlsson, Fredrik
    Engström, Eva
    Hallberg, Boubou
    Hansen-Pupp, Ingrid
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hyperglycemia in extremely preterm infants: insulin treatment, mortality and nutrient intakes2018In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 200, p. 104-110Article in journal (Refereed)
    Abstract [en]

    Objective: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants.

    Study design: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data.

    Results: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05).

    Conclusions: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

  • 565. Åkeson, Pia Karlsland
    et al.
    Åkesson, Kristina E
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vitamin D Intervention and Bone: A Randomized Clinical Trial in Fair- and Dark-skinned Children at Northern Latitudes2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 67, no 3, p. 388-394Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the study was to evaluate vitamin D status and effects of vitamin D intervention on bone mineral density (BMD) and content (BMC) in children with fair and dark skin in Sweden during winter.

    Methods: In a 2-center prospective double-blinded randomized intervention study 5- to 7-year-old children (n = 206) with fair and dark skin in Sweden (55 degrees N-63 degrees N) received daily vitamin D supplements of 25 mu g, 10 mu g, or placebo (2 mu g) during 3 winter months. We measured BMD and BMC for total body (TB), total body less head (TBLH), femoral neck (FN), and spine at baseline and 4 months later. Intake of vitamin D and calcium, serum 25-hydroxy vitamin D (S-25 [OH]D), and related parameters were analyzed.

    Results: Despite lower S-25(OH)D in dark than fair-skinned children, BMD of TB (P = 0.012) and TBLH (P = 0.002) and BMC of TBLH (P = 0.04) were higher at baseline and follow-up in those with dark skin. Delta (Delta) BMD and BMC of TB and TBLH did not differ between intervention and placebo groups, but FN-BMC increased more among dark-skinned children in the 25 mu g (P = 0.038) and 10 mu g (P = 0.027) groups compared to placebo. We found no associations between Delta S-25(OH)D, P-parathyroid hormone, P-alkaline phosphatase, and Delta BMD and BMC, respectively.

    Conclusions: BMD and BMC remained higher in dark- than fair-skinned children despite lower vitamin D status. Even though no difference in general was found in BMD or BMC after vitamin D intervention, the increase in FN-BMC in dark-skinned children may suggest an influence on bone in those with initially insufficient vitamin D status.

  • 566.
    Ångstrom-Brännström, Charlotte
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Engvall, G.
    Mullaney, T.
    Nilsson, K.
    Wickart-Johansson, G.
    Svärd, A. M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Facilitating Radiotherapy for Children: Technique, Design and Professional Care in Synergy, a Multicenter Intervention Study2016In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, p. S213-S213Article in journal (Other academic)
  • 567.
    Ångström-Brännström, Charlotte
    Umeå University, Faculty of Medicine, Department of Nursing.
    Långvarigt sjuka barn och tröst2013In: Palliativ vård: begrepp & perspektiv i teori och praktik / [ed] Birgitta Andershed, Britt-Marie Ternestedt, Cecilia Håkansson, Lund: Studentlitteratur, 2013, 1, p. 313-320Chapter in book (Other (popular science, discussion, etc.))
  • 568.
    Ångström-Brännström, Charlotte
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Engvall, Gunn
    Mullaney, Tara
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Nilsson, Kristina
    Wickart-Johansson, Gun
    Svärd, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0141086Article in journal (Refereed)
    Abstract [en]

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multi-center study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.

  • 569.
    Öhlund, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Serum lipid and apolipoprotein levels in 4-year-old children are associated with parental levels and track over time2011In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 65, no 4, p. 463-469Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: There are only a few studies linking dietary fat intake to serum lipid levels in young children. Our objective was to prospectively evaluate serum lipid levels from infancy to early childhood, and to explore their possible association with dietary, growth and parental factors.

    Subjects/Methods: Children (n=127) followed from early infancy were examined for serum lipid levels, anthropometry and dietary intake at 4 years of age. We also studied possible associations with parental anthropometric and blood biochemistry data collected from 122 mothers' and 118 fathers' when children were 4 years of age.

    Results: Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and the apolipoprotein B/apolipoprotein A-1 ratio (apo B/apo A-1) showed significant tracking from infancy to 4 years. Furthermore, children's TC levels correlated with paternal TC level from 6 months to 4 years, but with maternal only at 4 years. In girls, both LDLC and HDLC correlated with parental LDLC and HDLC. In all children, intake of saturated fatty acids (SAFAs) was higher than recommended, and in 90% of the children polyunsaturated fatty acid (PUFA) intake was lower than recommended.

    Conclusions: Serum lipid levels values tracked from infancy to 4 years and were associated with parental values. Higher serum lipid levels at 4 years compared with 6-18 months of age may result from changes in the quality of dietary fat. We therefore suggest that intake of dietary fat in 4-year-old children should be more focused on quality. Furthermore, as there were strong associations between the child and parental serum lipid levels this supports the view that family-based rather than individual intervention is preferable.

  • 570.
    Öhlund, Inger
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    BMI at 4 years of age is associated with previous and current protein intake and with paternal BMI2010In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 64, no 2, p. 138-145Article in journal (Other academic)
    Abstract [en]

    Objectives:To evaluate possible associations between body mass index (BMI) at 4 years of age, current and previous dietary intakes and parental BMI.Methods:A follow-up of dietary intake and anthropometry in 127 4-year-old children corresponding to 54% of children who completed an initial intervention study at 18 months of age.Results:Fourteen percent of the girls and 13% of the boys were overweight (age-adjusted BMI>/=25) and 2% of the girls and 3% of the boys were obese (age-adjusted BMI>/=30). Thirty-four percent and 9% of the fathers and 19 and 7% of the mothers were overweight and obese, respectively. BMI at 6-18 months was a strong predictor of BMI at 4 years. Univariate regression analyses revealed that intake of protein in particular, and also of total energy and carbohydrates at 17/18 months and at 4 years, was positively associated with BMI at 4 years. Although BMI at 6-18 months was the strongest predictor of BMI at 4 years, in the final multivariate models of the child's BMI, protein intake at 17-18 months and at 4 years, energy intake at 4 years and the father's-but not the mother's-BMI were also independent contributing factors.Conclusions:Among these healthy children, BMI at 4 years of age tracked from 6 to 18 months of age and were associated with previous and current protein intake as well as parental BMI, particularly that of the father.

  • 571.
    Öhlund, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsland Åkeson, Pia
    Increased vitamin D intake differentiated according to skin color is needed to meet requirements in young Swedish children during winter: a double-blind randomized clinical trial2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 1, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Background: Dark skin and low exposure to sunlight increase the risk of vitamin D insufficiency in children. Objective: The aim of the study was to evaluate the amount of vitamin D needed to ascertain that most children >4 y of age attain sufficient serum25-hydroxyvitamin D [S-25(OH) D; i.e., >= 50 nmol/L] during winter regardless of latitude and skin color. Design: In a longitudinal, double-blind, randomized, food-based intervention study, 5- to 7-y-old children from northern (638 degrees N) and southern (558 degrees N) Sweden with fair (n = 108) and dark (n = 98) skin were included. Children, stratified by skin color by using Fitzpa-trick's definition, were randomly assigned to receive milk-based vitamin D-3 supplements that provided 2 (placebo), 10, or 25 mu g/d during 3 winter months. Results: Mean daily vitamin D intake increased from 6 to 17 mu g and 26 mu g in the intervention groups supplemented with 10 and 25 mu g, respectively. In the intention-to-treat analysis, 90.2% (95% CI: 81.1%, 99.3%) of fair-skinned children randomly assigned to supplementation of 10 mu g/d attained sufficient concentrations, whereas 25 mu g/d was needed in dark-skinned children to reach sufficiency in 95.1% (95% CI: 88.5%, 100%). In children adherent to the study product, 97% (95% CI: 91.3%, 100%) and 87.9% (95% CI: 76.8%, 99%) of fair-and dark-skinned children, respectively, achieved sufficient concentrations if supplemented with 10 mu g/d. By using 95% prediction intervals for 30 and 50 nmol S-25(OH) D/L, intakes of 6 and 20 mu g/d are required in fair-skinned children, whereas 14 and 28 mu g/d are required in children with dark skin. Conclusion: Children with fair and dark skin require vitamin D intakes of 20 and 28 mu g/d, respectively, to maintain S-25(OH) D >= 50 nmol/L, whereas intakes of 6 and 14 mu g/d, respectively, are required to maintain concentrations >= 30 nmol/L during winter.

  • 572.
    Öhlund, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Serum 25-Hydroxyvitamin D Levels in Preschool-Age Children in Northern Sweden Are Inadequate After Summer and Diminish Further During Winter2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 5, p. 551-555Article in journal (Refereed)
    Abstract [en]

    Background and Objective: Despite studies indicating that vitamin D intake among Swedish children does not meet the recommendation, little is known of their vitamin D status. The aim of the present study was to examine vitamin D status in preschool-age children in relation to vitamin D intake, season, body mass index, and skin color. Methods: Preschool-age children (n = 90; mean age 54 +/- 7.1 months), all living in northern Sweden (latitude 63 degrees north), half of them with fair skin, half with darker complexion, were recruited from well-baby clinics. The study group was examined first in August-September (late summer) and then the following January-February (winter). Skin type, vitamin D intake, anthropometrics, serum 25-hydroxyvitamin D (S-25[OH] D), and serum parathyroid hormone were assessed. Results: Mean +/- SD S-25(OH) Din summer and winter were 60 +/- 15 nmol/L and 55 +/- 16 nmol/L, respectively (P < 0.001). Fifteen percent and 10% had S-25(OH) D >= 75 nmol/L, and 25% and 40% had S-25(OH) D < 50 nmol/L, respectively. The mean vitamin D intake was higher in dark-skinned compared with fair-skinned children. In spite of this, S-25(OH) D in dark-skinned children was lower compared with fair-skinned children during both seasons. The dietary intake of vitamin D was positively associated with S-25(OH) D levels. Conclusions: Vitamin D status is inadequate in preschool-age children living in northern Sweden, especially in dark-skinned children and during the winter despite vitamin D intakes meeting the recommendations, prompting strategies to improve intake of vitamin D in this population.

  • 573.
    Öhlund, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Olsson, Cecilia
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Dietary shortcomings in children on a gluten-free diet2010In: Journal of human nutrition and dietetics (Print), ISSN 0952-3871, E-ISSN 1365-277X, Vol. 23, no 3, p. 294-300Article in journal (Refereed)
    Abstract [en]

    Background: Coeliac disease (CD), or permanent gluten intolerance, is one of the most common chronic food-related diseases among children in Europe and the USA. The treatment is lifelong gluten-free diet (GFD) (i.e. the exclusion of wheat, rye and barley from the diet, which are important sources particularly of iron, dietary fibre and vitamin B). The present study aimed to evaluate dietary intakes of energy and nutrients in children and adolescents on GFD and compare these with intake of comparable age groups on a normal diet as well as current recommendations.

    Methods: Thirty children, 4-17 years of age with confirmed CD and on GFD were agreed to participate in this study at the Department of Pediatrics, Umeå University Hospital. Weight and height were used to calculate individual energy requirement according to Nordic Nutrition Recommendations 2004 (NNR-04). Dietary intake was assessed using 5-day food records and household measures were used for quantities. Twenty-five children completed their dietary record.

    Results: Thirteen of the 25 children did not meet the recommended energy intake and the dietary intakes were inadequate regarding quality of macronutrients and quantity of minerals and vitamins. The mean intakes of sucrose and saturated fatty acids were above and the intakes of dietary fibre, vitamin D, magnesium and selenium below the NNR-04. High intakes of sucrose and saturated fat and a low intake of dietary fibre were also noted in a previous national survey on healthy children on a normal diet. The nutrient density of vitamin D, riboflavin, niacin, thiamine, magnesium and selenium were lower among CD children than healthy children but, for iron and calcium, it was higher in CD children.

    Conclusions: Children on GFD appear to follow the same trends as healthy children on a normal diet, with high intakes of saturated fat and sucrose and low intakes of dietary fibre, vitamin D and magnesium compared to recommendations.

  • 574. Örtqvist, Å
    et al.
    Blennow, M
    Carlsson, R-M
    Hansson, LÅ
    Lindberg, A
    Lindqvist, I
    Magnusson, M
    Nilsson, L
    Norlund, A
    Nyrén, O
    Olcén, P
    Olin, P
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Säwe, J
    Söderström, A
    Trollfors, B
    Vaccination of children: a children systematic review2010In: Acta Paediatrica. Supplement, ISSN 0803-5326, Vol. 99, no s461, p. 1-192Article in journal (Refereed)
  • 575. Østergaard, Lars
    et al.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berglund, Johan
    Flodmark, Carl-Erik
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bianco, Veronique
    Baine, Yaela
    Miller, Jacqueline M.
    A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix(®) in subjects aged 11-17 years: An open, randomised, controlled trial.2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 4, p. 774-783Article in journal (Refereed)
    Abstract [en]

    The co-administration of the tetravalent meningococcal conjugate vaccine, MenACWY-TT, with a licensed hepatitis A and B vaccine, HepA/B (Twinrix(®)), was compared to their separate administration in this open, randomised, controlled study. Healthy subjects 11-17 years of age (n=611) were randomised (3:1:1) to receive both vaccines, MenACWY-TT alone or HepA/B alone. The co-administration of both vaccines was shown to be non-inferior to their individual administration. At seven months after the first vaccination, 99.4-100% of the subjects who received both vaccines co-administered showed seroprotection against all meningococcal serogroups and at least 99.1% of them were seropositive for hepatitis A and seroprotected against hepatitis B. This study suggests that MenACWY-TT vaccine could be co-administered with HepA/B without adversely impacting the immunogenicity, safety and reactogenicity of either of the vaccines.

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